Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hemostatic survey was done on 14 Bedlington terriers, 13 of which have the recently discovered copper toxicosis. Their hepatic copper ranged from 109 to 9,888 microgram/g dry weight and their ages from 8 months to 8 years. Despite histologic evidence of hepatitis in younger dogs and cirrhosis in older ones, plasmatic coagulation factors were not depressed. In fact, the hemophilic factors VIII, IX and XI were above normal, more closely related to the age of the dog than to the hepatic copper. Furthermore, their platelet were unusually sensitive to adenosine diphosphate exposure. Offsprings of matings between Bedlington terriers and Beagles seem to be normal.
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PMID:Hemostasis in the copper-laden Bedlington terrier: a possible model of Wilson's disease. 737 1

Long-Evans Cinnamon (LEC) rats, characterized by a gross accumulation of hepatic Cu and the spontaneous onset of hepatitis, have been established to be an animal model for Wilson disease. They were used to estimate the relationships among copper (Cu), metallothionein (MT), and reduced glutathione (GSH) in biliary excretion in this study. Even though a huge amount of MT existed in the LEC rat liver (5016 micrograms/g liver) compared to that (63 micrograms/g liver) of controls (Fischer rats), the biliary excretion of MT (65 ng/ml bile) did not reflect the accumulated MT level in LEC rats. It seems likely that MT does not excrete intrinsically into the bile. Biliary excretion of Cu (0.17 microgram/ml) in LEC rats was significantly lower than that (0.57 microgram/ml) in Fischer rats. The difference in biliary excretion of GSH between the two groups was significant but slight. The reduced excretion of GSH into bile in LEC rats may be due to increased hepatic gamma-glutamyltransferase but not to hepatic GSH levels. There were no differences in biliary potassium and inorganic phosphorous between the two groups. On the other hand, excretion of lysosomal enzymes such as beta-N-acetylglucosaminidase into bile was much lower in LEC rats (15.6 units/liter) than in controls (42.5 units/liter). The defective biliary excretion of Cu may be due to impaired lysosomal exocytosis, rather than canalicular membrane impairment. The LEC rat is very useful for research into the dynamics of metal excretion via the hepatobiliary system.
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PMID:Biliary excretion of copper, metallothionein, and glutathione into Long-Evans Cinnamon rats: a convincing animal model for Wilson disease. 755 24

1. The anti-inflammatory and hepatoprotective efficacy of CuPu(Py)2 ((N,N'-bis(2-pyridyl-methylene)-1,4-butanediamine) (N,N',N",N")-Cu2+), a serum-stable, copper-di-Schiffbase active centre analogue of Cu2Zn2 superoxide dismutase was tested in male NMNR mice suffering from endotoxin/galactosamine-induced hepatitis. 2. Parameters including the activities of serum transaminases and sorbitol-dehydrogenase as well as the levels of reactive oxygen and nitrogen intermediates which were used to quantify the disease activity. 3. A dose-dependent inhibition of hepatic enzyme release was noted in the presence of 0.1-10 mg/kg of CuPu(Py)2. 4. The release of transaminases from damaged liver cells was reduced by 68% and paralleled the reduction of serum levels of nitric oxides. 5. Elevated levels of reactive oxygen species were normalized to those healthy controls. 6. The copper-free apochelate Pu(Py)2, which is unable to dismutate superoxide, did not display any anti-inflammatory reactivity.
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PMID:Hepatoprotective reactivity of a copper-di-Schiffbase active centre analogue of Cu2Zn2 superoxide dismutase. 759 Jan 16

Random samples of urine from control subjects, and subjects treated with methadone (an agonist of morphine) for drug addiction, were analyzed for calcium and trace elements zinc and copper. The following differences (based on creatinine) were observed between the two groups: Calcium excretion did not show any significant differences between the two groups (146 mmg/g creatinine vs. 135 mg/g creatinine vs. 33 +/- 3 micrograms/g creatinine in controls). However, the excretion of copper in drug addicts diminished (23 +/- 3 micrograms/g creatinine in controls; p < 0.05), while that of zinc was excessive (600 +/- 50 micrograms/g creatinine vs. 300 +/- 30 micrograms/g creatinine in controls; p < 0.001). The ever increasing link between zinc and immunity and the fact that drug addicts are susceptible to various infections such as hepatitis and acquired immuno deficiency syndrome raises concern about the excessive urinary loss of zinc in this group and calls for further investigations such as balance studies and intervention if necessary.
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PMID:Excessive urinary excretion of zinc in drug addicts: a preliminary study during methadone detoxification. 759 15

We report the pattern of childhood liver disease revealed by a study of 134 biopsies obtained from 128 infants and children below the age of 16 years seen in this hospital during a 3-year period. The most common histological diagnoses were neonatal hepatitis syndrome in 23, storage disorders in 11, and cirrhosis in 26 children. Less common diagnoses included Reye's syndrome in four, fatty liver in seven, granulomas in four, and chronic active hepatitis, fulminant hepatitis, congenital hepatic fibrosis and neoplasms in two children each. Miscellaneous specific diagnoses were made in 16 cases. Twenty-three per cent of the liver biopsies were non-diagnostic. The study has provided background information on the occurrence of specific histological diagnoses in liver biopsies in infants and children in this tropical region and identifies a group with cirrhosis and copper deposition which was not typical of either Indian childhood cirrhosis or Wilson's disease.
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PMID:The pattern of liver disease in Indian children: a review of 128 biopsied cases. 768 12

LEC rats develop disorder of cooper metabolism and hepatitis similar to those of human Wilson's disease. We recently demonstrated that the gene responsible for hepatitis (hts) of LEC rats is homologous to Wilson's disease gene (WD). The present study showed a deletion of at least 90 base pair of WD cDNA in LEC rats, which corresponds to nucleotides 3981 to 4071 in human WD cDNA sequence. This deletion was linked with hepatic copper accumulation and hepatitis, and considered to be a primary mutation for hepatic disorder in the LEC rat. The WD gene was assigned to rat chromosome 16 at band q12.2-q12.4 by fluorescence in situ hybridization (FISH).
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PMID:Deletion of the Wilson's disease gene in hereditary hepatitis LEC rats. 777 79

Long-Evans rats with a cinnamon-like coat color (LEC) is an inbred strain accumulating copper (Cu) in the liver abnormally and showing spontaneous hepatitis and hepatoma. The present study was intended to clarify how Cu accumulates in the LEC rat liver. For this purpose, the distribution profiles of Cu and zinc (Zn) and the inducibility of metallothionein (MT) synthesis were examined in the liver between Cu-loaded Long Evans agouti (LEA, the original strain of LEC) rats and were compared with those in control LEC rats. LEA rats (female, five weeks old) were injected subcutaneously with CuCl2 daily at a dose of 3 mg Cu/kg body weight for 2, 4, 6, and 9 days. The concentration of Cu (124 micrograms/g) accumulated in the LEA rat liver after four injections was comparable to that in control LEC rats. Only 20% of Cu in the liver of LEA rats was recovered in the supernatant fraction in the form of MT, while Cu in the LEC rat liver (113 micrograms/g) was recovered mostly in the supernatant fraction, and was bound to MT. Although the increased concentration of Cu in the LEA rat liver was further elevated after additional injections of Cu, the amount of MT did not increase further. The MT mRNA content in the LEA rat liver remained lower than that of LEC rats even after further injections of Cu. Therefore, the present results suggest that LEC rats can accumulate Cu at a high concentration in the liver because of their extremely high inducibility of MT.
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PMID:Enhanced synthesis of metallothionein as a possible cause of abnormal copper accumulation in LEC rats. 779 93

Long-Evans Cinnamon (LEC) rats are characterized by the sudden onset of hepatitis around 4 months after birth and the gross accumulation of hepatic copper (Cu) accompanied by metallothionein (MT). The biliary excretion of manganese (Mn) and cadmium (Cd) injected intravenously was studied in 3-month-old LEC rats without signs of hepatitis. Injected Mn was excreted into the bile in LEC and Fischer rats used for comparison. However, increased biliary excretion of Cd was found not in the LEC rat but in the Fischer rat. Excretion of horseradish peroxidase (HRP) injected along with the metal mixture was significantly lower in the LEC group than in the Fischer group. Our results suggest that Mn excretion is not related to the existence of a gross amount of Cu-MT. Reduced excretion of Cd may be partly due to binding to Cu-MT in the liver. Decreased excretion of HRP implies the existence of an inherent defect in the bile excretion route for endo- and exogenous substances.
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PMID:Biliary excretion of exogenous cadmium and manganese in Long-Evans Cinnamon (LEC) rats characterized by an inherently gross amount of copper-metallothionein in the liver. 780 94

Wilson's disease is an hereditary recessive autosomal disorder which affects around five people per million inhabitants. The primary defect is localized in the liver and the disease is manifested by the accumulation of copper in tissues. The diminution of ceruloplasmin, which until a few years ago was mistakenly thought to be the pathogenetic cause of Wilson's disease, is an epiphenomenon of the underlying metabolic defect characterized by defective copper biliary excretion. There are four stages in the natural history of the disease: 1) an asymptomatic stage of hepatic copper accumulation; 2) dismission and redistribution of copper leading to hepatocellular necrosis and hemolysis; 3) extrahepatic accumulation of copper leading to the onset of cirrhosis and neurological damage; 4) stage of homeostasis following treatment but with possible irreversible neurological damage. Treatment of Wilson's disease takes the form of pharmacological, dietary and surgical therapy. Through the formation of copper and protein metal complexes D-penicillamine impoverishes copper deposits causing the reduction or disappearance of hepatic and neurological symptoms; a small percentage of patients treated develops a nephrotic syndrome requiring the compulsory suspension of the drug. In this case a valid alternative is triethylenetetramine dichlorohydrate (TETA) which provokes increased blood copper during copper diuresis. The response to pharmacological treatment is better the earlier treatment is started and the more regular its administration. Dietary intake of copper must be reduced in parallel avoiding foods with a high copper content. Liver transplant obviously leads to the "resolution" of the underlying metabolic problem in patients who develop fulminating hepatitis with hypercupremia and hemolysis and, of course, in cases of uncompensated cirrhosis which do not respond to chelating therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Wilson's disease: physiopathology, therapeutic approach and case report]. 784 48

LEC rats develop an autosomal recessive hepatitis and subsequently liver cancer associated with copper accumulation in the liver similar to that of Wilson's disease. Using 71 backcross [(WKAH x LEC) x LEC] rats, linkage analysis of the hepatitis with the WD gene for Wilson's disease revealed identical segregation and no recombination event between these two genes. This result indicates that the WD gene is a prime candidate for the hts gene responsible for the hepatitis of LEC rats, and suggests that the hepatitis of LEC rats may be caused by a defect in a copper-transporting ATPase expressed in the liver.
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PMID:The WD gene for Wilson's disease links to the hepatitis of LEC rats. 792 21


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